Stationary and Progressive Phenotypes Caused by the p.G90D Mutation in Rhodopsin Gene

Kobal, Nina; Krašovec, Tjaša; Šuštar, Maja; Volk, Marija; Peterlin, Borut; Hawlina, Marko; Fakin, Ana

doi:10.3390/ijms22042133

Cited by 7 publications

(6 citation statements)

References 50 publications

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Section: Discussionmentioning

confidence: 79%

“…Previous descriptions of AD CSNB revealed no association with myopia, nystagmus, and amblyopia unlike other types of CSNB [ 9 , 10 , 11 , 12 ]. Similar to the Slovenian cohort with AD CSNB caused by RHO variants with 20/20 visual acuity, patient 1 had good visual acuity ( Table 5 ) [ 9 ]. Patient 1′s myopia of −3.75 and −3.25 diopters was in the range of average myopia in Taiwan and does not seem related to the diagnosis of AD CSNB ( Table 5 ) [ 13 ].…”

Section: Discussionmentioning

confidence: 79%

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Congenital Stationary Night Blindness: Clinical and Genetic Features

Kim

Liu

Chang

et al. 2022

IJMS

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Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert–Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype–phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype–phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 79%

Congenital Stationary Night Blindness: Clinical and Genetic Features

Kim

Liu

Chang

et al. 2022

IJMS

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“…It is possible that CNGA3 and CNGB3 cause a spectrum of disorders between stationary progressive disease with different rates of progression, where different variants or other cis/trans factors affect disease expression. For example, RHO variants may cause stationary (congenital stationary night blindness) or progressive disease (retinitis pigmentosa) even within the same family [48]. It remains to be answered whether the same is true for CNGA3/CNGB3.…”

Section: Cnga3/cngb3 Retinopathy Is Predominantly a Progressive Diseasementioning

confidence: 99%

Disease Progression in CNGA3 and CNGB3 Retinopathy; Characteristics of Slovenian Cohort and Proposed OCT Staging Based on Pooled Data from 126 Patients from 7 Studies

Pompe

Vrabič

Volk

et al. 2021

CIMB

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Achromatopsia has been proposed to be a morphologically predominately stable retinopathy with rare reports of progression of structural changes in the macula. A five-grade system of optical coherence tomography (OCT) features has been used for the classification of structural macular changes. However, their association with age remains questionable. We characterized the Slovenian cohort of 12 patients with pathogenic variants in CNGA3 or CNGB3 who had been followed up with OCT for up to 9 years. Based on observed structural changes in association with age, the following four-stage classification of retinal morphological changes was proposed: (I) preserved inner segment ellipsoid band (Ise), (II) disrupted ISe, (III) ISe loss and (IV) ISe and RPE loss. Data from six previously published studies reporting OCT morphology in CNGA3 and CNGB3 patients were additionally collected, forming the largest CNGA3/CNGB3 cohort to date, comprising 126 patients aged 1–71 years. Multiple regression analysis showed a significant correlation of OCT stage with age (p < 0.001) and no correlation with gene (p > 0.05). The median ages of patients with stages I–IV were 12 years, 23 years, 27 years and 48 years, respectively, and no patient older than 50 years had continuous ISe. Our findings suggest that achromatopsia presents with slowly but steadily progressive structural changes of the macular outer retinal layers. However, whether morphological changes in time follow the proposed four-stage linear pattern needs to be confirmed in a long-term study.

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“…Most patients with the G90D mutation express normal amounts of rhodopsin, and the structure of the rods is well preserved ( Sieving et al, 1995 ), while others exhibit the typical RP manifestation, in which the loss of rods is accompanied by the subsequent death of the cone cells and blindness ( Berson, 1993 ). A cohort study comprised of 15 patients showed that 20 and 53.3% of patients with the G90D mutation displayed CSNB and classic RP, respectively, with no obvious sex differences ( Kobal et al, 2021 ). Recently, slow retinal degeneration was also found in homozygous G90D transgenic mice ( Colozo et al, 2020 ).…”

Section: Mechanisms Of Rhodopsin-related Retinal Disordersmentioning

confidence: 99%

Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies

et al. 2023

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Rhodopsin is a light-sensitive G protein-coupled receptor that initiates the phototransduction cascade in rod photoreceptors. Mutations in the rhodopsin-encoding gene RHO are the leading cause of autosomal dominant retinitis pigmentosa (ADRP). To date, more than 200 mutations have been identified in RHO. The high allelic heterogeneity of RHO mutations suggests complicated pathogenic mechanisms. Here, we discuss representative RHO mutations as examples to briefly summarize the mechanisms underlying rhodopsin-related retinal dystrophy, which include but are not limited to endoplasmic reticulum stress and calcium ion dysregulation resulting from protein misfolding, mistrafficking, and malfunction. Based on recent advances in our understanding of disease mechanisms, various treatment methods, including adaptation, whole-eye electrical stimulation, and small molecular compounds, have been developed. Additionally, innovative therapeutic treatment strategies, such as antisense oligonucleotide therapy, gene therapy, optogenetic therapy, and stem cell therapy, have achieved promising outcomes in preclinical disease models of rhodopsin mutations. Successful translation of these treatment strategies may effectively ameliorate, prevent or rescue vision loss related to rhodopsin mutations.

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Stationary and Progressive Phenotypes Caused by the p.G90D Mutation in Rhodopsin Gene

Cited by 7 publications

References 50 publications

Congenital Stationary Night Blindness: Clinical and Genetic Features

Congenital Stationary Night Blindness: Clinical and Genetic Features

Disease Progression in CNGA3 and CNGB3 Retinopathy; Characteristics of Slovenian Cohort and Proposed OCT Staging Based on Pooled Data from 126 Patients from 7 Studies

Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies

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